Nonalcoholic Fatty Liver Disease: New Treatments

Timothy Hardy; Quentin M. Anstee; Christopher P. Day

Disclosures

Curr Opin Gastroenterol. 2015;31(3):175-183. 

In This Article

Abstract and Introduction

Abstract

Purpose of review Nonalcoholic fatty liver disease is the most common cause of liver dysfunction in the western world because of its close association with obesity, insulin resistance and dyslipidaemia. Nonalcoholic steatohepatitis (NASH) is a particular health concern due to the increased morbidity and mortality associated with progressive disease. At present, without specific targeted pharmacological therapies, the mainstay of therapy remains weight loss through dietary modification and lifestyle change; thus, the purpose of this review is to summarize the recent evidence for current and emerging therapies in NASH.

Recent findings Some existing medications, including pioglitazones and angiotensin receptor antagonists, may be repurposed to help treat this condition. Vitamin E may improve histology in NASH, but safety issues limit its use. Recently, a number of novel agents specifically targeting nonalcoholic fatty liver disease pathogenesis have entered clinical trials, including the farnesoid X receptor agonist obeticholic acid, which has shown significant histological improvements in steatohepatitis and fibrosis.

Summary Diet/lifestyle modification remains the mainstay of treatment. For patients with NASH and advanced fibrosis, current liver-directed pharmacotherapy with vitamin E and pioglitazone offer some benefits; obeticholic acid appears promising and is currently being tested. Comorbidities must be diagnosed and treated; cardiovascular disease remains a primary cause of death in these patients.

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction in the western world[1] because of its close association with obesity, insulin resistance and dyslipidaemia; it is therefore considered the hepatic manifestation of the metabolic syndrome. A particular health concern is patients with nonalcoholic steatohepatitis (NASH) with accompanying hepatocellular injury that can lead to progressive liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) as well as increased cardiovascular risk.[1] At present, there is no approved therapy for NASH and the optimal treatment remains uncertain; effective therapies are thus a research priority to reduce the anticipated burden of liver disease.

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